The goals of this project are to develop and characterize arterial spin labeling (ASL) as a tool for functional magnetic resonance imaging (fMRI), and to determine under what conditions ASL is preferable to blood oxygenation dependent contrast (BOLD) for fMRI. ASL is a noninvasive technique for imaging of cerebral blood flow (CBF) that uses radio frequency pulses to tag arterial blood by magnetic inversion. The inflow of tagged blood is observed by MRI, and provides a signal that is closely related to CBF. The quantitation of CBF using ASL has been a focus of research in this laboratory over the past several years. While this has greatly improved CBF quantitation, there remain significant sources of error and discrepancies between ASL techniques that are not understood. One specific aim of this work is to further improve the quantitation of CBF using ASL, focusing on three potentially significant but relatively unexplored areas: laminar flow related dispersion of the tag bolus; differences between global and local CBF changes; and cardiac modulation of the ASL signal. Applications of quantitative ASL include direct medical applications such as diagnosis, evaluation of treatment, and risk assessment for stroke, the study of fMRJ contrast mechanisms, and quantitative fMRI, all of which will benefit from the developments of this specific aim. A new area of research is to explore the use of non-quantitative ASL for fMRI brain mapping. In quantitative ASL, a significant amount of sensitivity is sacrificed in order to achieve insensitivity to several major sources of systematic errors. The major disadvantage of ASL relative to BOLD for brain mapping is that it is significantly less sensitive, while the main advantage of ASL is that the spatial localization of the ASL signal to brain tissue (and presumably to the site of brain activity) is thought to be better than for BOLD fMRI The second specific aim of this work is to develop new ASL techniques that maximize the sensitivity to brain activation without regard for CBF quantitation, and the third specific aim is to test the hypothesis that the functional ASL signal is better localized to gray matter than BOLD.